CN108143800B - Traditional Chinese medicine composition for treating hypertensive heart failure - Google Patents

Traditional Chinese medicine composition for treating hypertensive heart failure Download PDF

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CN108143800B
CN108143800B CN201810146679.3A CN201810146679A CN108143800B CN 108143800 B CN108143800 B CN 108143800B CN 201810146679 A CN201810146679 A CN 201810146679A CN 108143800 B CN108143800 B CN 108143800B
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张国华
陈凯
黄裕
刘馨
庄宇鑫
管怡晴
党文振
马韵词
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Southern Medical University
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Abstract

The invention discloses a traditional Chinese medicine composition for treating hypertension and heart failure, and belongs to the field of traditional Chinese medicines. The raw material medicines of the traditional Chinese medicine composition comprise caulis spatholobi, pseudo-ginseng, salvia miltiorrhiza, astragalus mongholicus and pummelo peel. The traditional Chinese medicine composition accords with the theory of modern systemic pharmacology, and the selected medicine has definite components which can act on disease targets of hypertension and heart failure simultaneously; meanwhile, the Chinese medicinal composition conforms to the traditional Chinese medicine dialectical theory system and the monarch, minister, assistant and guide compatibility principle of the traditional Chinese medicine. In vivo experiment results show that the traditional Chinese medicine composition can effectively reduce the systolic pressure of spontaneous hypertensive rat SHR, and the effect is slightly lower than that of positive control drug captopril; meanwhile, the ejection fraction and the short axis shortening rate of the SHR heart can be improved, and the treatment effect is better than that of captopril. The traditional Chinese medicine composition has the advantages of few medicinal ingredients, definite and reliable curative effect and definite main medicinal components, can reduce non-medicinal effect factors in a traditional Chinese medicine compound preparation, and improves the preparation level.

Description

Traditional Chinese medicine composition for treating hypertensive heart failure
Technical Field
The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating hypertensive heart failure.
Background
Hypertension is a common disease and frequently encountered disease, the disease generally has slow onset, and patients often have no symptoms in early stage or only have symptoms of dizziness, headache, palpitation, tinnitus and the like. Hypertension, if poorly controlled for long periods of time, can cause structural and functional changes in the heart, known as hypertensive heart disease, including: early-stage hypodiastolic function of the left ventricle and left ventricular hypertrophy, the progressive occurrence of hypomyocardial contractility finally leads to heart failure, and 70 percent of the heart failure is caused by hypertension. Hypertension heart failure is more common than heart failure caused by endocardial infection or arrhythmia, has serious symptoms and is difficult to reverse, and most of the hypertension heart failure treatment cannot be satisfied by using antihypertensive drugs or cardiotonic drugs singly.
In recent years, the medicine and surgical treatment of heart failure are greatly improved, a more systematic treatment scheme is provided clinically, the morbidity and the mortality cannot be reduced ideally, and the large-scale clinical application of the medicine and the surgical treatment in the heart failure treatment is limited due to the side effect of western medicines and relatively high treatment cost, so that the long-term clinical treatment is difficult to complete. Therefore, the seeking of a treatment method and a medicine with definite clinical curative effect and small safety and toxic and side effects are always paid attention to by clinicians in various countries, so that people turn to a treatment method of traditional Chinese medicine.
In traditional Chinese medicine, the compound traditional Chinese medicine is an important form of traditional Chinese medicine for treating diseases, can exert the advantages of traditional Chinese medicine syndrome differentiation and has the function of multidirectional regulation. However, the compound traditional Chinese medicine is various and complex in components and unclear in action mechanism, so that the compound traditional Chinese medicine with a definite curative effect is searched by combining modern pharmacology and a traditional Chinese medicine syndrome differentiation system, and the compound traditional Chinese medicine has an important significance for traditional Chinese medicine treatment of hypertension and heart failure.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine composition for treating hypertension and/or heart disease, in particular to hypertensive heart failure in hypertensive heart disease and a preparation method thereof.
The technical scheme adopted by the invention is as follows:
a Chinese medicinal composition comprises caulis Spatholobi, Notoginseng radix, Saviae Miltiorrhizae radix, radix astragali, and exocarpium Citri Grandis.
Preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 10-20 parts of caulis spatholobi, 2-8 parts of pseudo-ginseng, 5-15 parts of salvia miltiorrhiza, 10-20 parts of astragalus membranaceus and 5-15 parts of pummelo peel.
Preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 12-18 parts of caulis spatholobi, 4-6 parts of pseudo-ginseng, 7-13 parts of salvia miltiorrhiza, 12-18 parts of astragalus membranaceus and 7-13 parts of pummelo peel.
Preferably, the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 15 parts of caulis spatholobi, 5 parts of pseudo-ginseng, 10 parts of salvia miltiorrhiza, 15 parts of astragalus mongholicus and 10 parts of pummelo peel.
Preferably, the active ingredient of the raw material drug is an extract of methanol aqueous solution, and is subjected to ultrasonic treatment again.
Preferably, the traditional Chinese medicine composition is used for treating hypertension and/or heart disease. The traditional Chinese medicine composition is developed aiming at hypertensive heart disease, particularly hypertensive heart failure, but hypertensive heart disease is a heart disease caused by poor long-term control of hypertension, has the dual characteristics of hypertension and heart disease, and is more difficult to treat. Based on the above, the traditional Chinese medicine composition can also be suitable for general hypertension, or heart disease, or prevention and treatment of hypertensive heart disease.
Preferably, the heart disease is hypertensive heart disease. Hypertensive heart disease includes hypertensive heart failure, myocardial fibrosis, arrhythmia, and the like.
Preferably, the hypertensive heart disease is hypertensive heart failure.
Preferably, the dosage form of the traditional Chinese medicine composition is any one of the dosage forms in pharmaceutics. Can be prepared into required dosage forms by adding different auxiliary materials.
Preferably, the dosage form comprises decoction, pills, powder, oral preparations, tablets, granules and capsules.
The Chinese medicinal composition for treating hypertensive heart disease, in particular hypertensive heart failure, comprises the following medicinal materials:
caulis spatholobi: dried rattan stem derived from Spatholobus suberectus Dunn of Leguminosae; sweet and bitter in taste, neutral in nature, and capable of entering heart and spleen channels, and has the effects of promoting blood circulation, tonifying blood, regulating menstruation, relieving pain, relaxing muscles and tendons, and activating collaterals.
Pseudo-ginseng: dried root and rhizome of Panax notoginseng (Burk.) F.H.Chen) belonging to Araliaceae; sweet and slightly bitter taste, warm nature, heart and liver meridian entered, and has effects of dispelling blood stasis, stopping bleeding, detumescence and relieving pain.
Red sage root: is derived from dried root and rhizome of Salvia Miltiorrhiza bge of Labiatae; bitter in taste and slightly cold in nature, and has the effects of activating blood circulation to dissipate blood stasis, stimulating the menstrual flow to relieve pain, cooling blood and eliminating carbuncle, and the like, and enters heart and liver channels.
Astragalus root: dried root derived from Astragalus membranaceus bge. of Leguminosae (Fisch.) Astragalus membranaceus bge. var. mongholicus (Beg.) Hsiao or Astragalus membranaceus bge. A. membranaceus bge. Bge.; sweet taste, warm nature, heart, lung and spleen meridians entered, and has the effects of invigorating qi, consolidating superficial resistance, arresting sweating, relieving depletion, inducing diuresis and relieving swelling.
Pummelo peel: immature or near-mature dried outer pericarp derived from Osbeck of Citrus grandis, Tomentosa7 or Citrus grandis (L.) of Rutaceae; pungent and bitter in flavor and warm in nature, and has the effects of regulating qi, relieving epigastric distention, eliminating dampness and resolving phlegm.
In the traditional Chinese medicine, the heart failure belongs to the categories of chest stuffiness, palpitation, severe palpitation, asthma, edema, phlegm and retained fluid and the like, and the inventor considers that the pathogenesis of the heart failure mainly comprises blood stasis, qi deficiency and phlegm dampness according to the diagnosis and treatment analysis of the traditional Chinese medicine, and further determines the main treatment method for the heart failure by activating blood, tonifying qi and reducing phlegm.
The inventor sets out a batch of traditional Chinese medicines capable of simultaneously acting on hypertension and heart failure from a traditional Chinese medicine system pharmacological database and an analysis platform (TCMSP) based on modern pharmacological research of the traditional Chinese medicines, wherein the TCMSP is a traditional Chinese medicine system pharmacological database and an analysis platform integrating pharmacokinetics, medicinal chemistry and a medicament-target protein-disease network, the database collects 500 traditional Chinese medicines in 2010 version traditional Chinese medicine pharmacopeia, obtains 30069 compounds contained in each traditional Chinese medicine through document mining and database integration, obtains target protein information of the traditional Chinese medicine molecules through model prediction and existing experimental data, further combines a drug bank, TTD, HIT and other databases to obtain target protein and disease information thereof, finally forms a ' medicament-molecule-target-disease ' network for each stasis traditional Chinese medicine, the inventor respectively analyzes traditional Chinese medicine data corresponding to ' hypertension ' and ' heart failure ' and obtains traditional Chinese medicine data for simultaneously acting on hypertension and heart failure, the selected traditional Chinese medicine components have definite target points of the blood stasis of the traditional Chinese medicines and the blood stasis-target points of the ' hypertension ' and the heart failure ', the inventor respectively analyzes the traditional Chinese medicine composition for simultaneously acting on hypertension and the heart failure according to the principle of qi deficiency, the theory of the traditional Chinese medicine, the hypertension and the hypertension, the hypertension and the hypertension, the hypertension and the hypertension are finally obtained by the formula of the salvia miltiorrhiza, the formula, the hypertension and the hypertension are obtained by the formula of the hypertension and the hypertension are selected by the formula, the formula of the monarch, the formula of the hypertension are selected by the formula, the formula of the hypertension and the monarch principle of the formula of the monarch and the formula, the formula of the monarch principle of the monarch and the monarch, the.
Under the inspiration of the composition, the reasonable blending of the components and the parts by weight of the monarch drug and the monarch drug is included in the protection scope of the invention according to the theory of traditional Chinese medicine and the identification of the physique of patients. In addition, under the condition of not violating the principle of the traditional Chinese medicine theory, a small amount of adjuvant drugs and guiding drugs are properly added according to the needs, and the invention is included in the protection scope.
The invention is suitable for treating hypertension and heart failure, and the following cases need to be taken with cautions or under the guidance of doctors, ① pregnant women, ② women who have no blood stasis during menstrual period and bleeding, ③ patients who have yin deficiency and fire excess based on traditional Chinese medicine syndrome differentiation, and ④ patients who have liver and kidney insufficiency.
A preparation method of a traditional Chinese medicine composition comprises the following steps:
1) pulverizing caulis Spatholobi, Notoginseng radix, Saviae Miltiorrhizae radix, radix astragali and exocarpium Citri Grandis as raw materials of the Chinese medicinal composition;
2) adding 40% -50% v/v methanol aqueous solution 6-12 times the volume of the Chinese medicinal composition, heating, refluxing, extracting for 1-1.5h, and cooling to room temperature;
3) subjecting the extractive solution to ultrasonic treatment at power of 600-800W, frequency of 40-50KHz and temperature of 40-50 deg.C for 50-60min, and cooling to room temperature;
4) taking the supernatant, centrifuging at 3000-;
according to the requirement, a proper amount of auxiliary materials are added to prepare the traditional Chinese medicine composition with any dosage form.
According to the principle of "similar solubility", a lipophilic solvent is selected for lipophilic components to be extracted, and water and a hydrophilic solvent are selected for hydrophilic components to be extracted. Although methanol is a hydrophilic solvent and can be freely mixed with water, a plurality of lipophilic components can be dissolved in the methanol, so that the methanol extraction solution contains both water-soluble components and fat-soluble components. Water can be added into methanol to prepare methanol water solutions with different concentrations, and alcohol with proper concentration can be selected for extraction according to the condition of extraction components. The inventor finds that the traditional Chinese medicine composition contains more fat-soluble components and has partial water-soluble components, so that the components in the traditional Chinese medicine composition are obtained to the maximum extent by adopting an alcohol extraction and ultrasonic extraction method.
The invention has the beneficial effects that:
(1) the traditional Chinese medicine composition provided by the invention conforms to the theory of modern system pharmacology, the selected medicines have clear components and can simultaneously act on disease targets of hypertension and heart failure (including angiotensin II receptor type 1, angiotensin converting enzyme, β adrenergic receptor and the like), and simultaneously the traditional Chinese medicine syndrome differentiation theory system and the monarch, minister, assistant and guide compatibility principle of traditional Chinese medicines are also conformed, wherein the salvia miltiorrhiza, the panax notoginseng and the caulis spatholobi are monarch medicines and can activate blood and remove stasis, the astragalus membranaceus and the exocarpium citri rubrum are ministerial medicines, the astragalus membranaceus can tonify heart qi, the exocarpium citri grandis can eliminate phlegm and promote diuresis, and the pathological states of hypertension and heart failure with blood stasis, qi deficiency and phlegm dampness can be.
(2) The traditional Chinese medicine composition has a definite effect of treating hypertension and heart failure: in vivo experiment results show that the traditional Chinese medicine composition can effectively reduce the systolic pressure of Spontaneous Hypertensive Rats (SHR), and the effect is slightly lower than that of a positive control drug captopril; meanwhile, the ejection fraction and the short axis shortening rate of the SHR heart can be improved, and the treatment effect is better than that of captopril.
(3) Compared with other compound traditional Chinese medicines, the components of the traditional Chinese medicine composition have the advantages of less medicinal ingredients, definite and reliable curative effect and definite main medicinal property components, can reduce non-medicinal effect factors in a traditional Chinese medicine compound preparation, and improve the preparation level.
Drawings
FIG. 1: the systolic blood pressure of each group of rats [ graph,. indicates P <0.05vs. shr,. indicates P <0.01vs. shr,. indicates P <0.001vs. shr ];
FIG. 2: serum Nitric Oxide (NO) content of rats in each group [ in the figure, [ P <0.05vs. shr, [ P <0.01vs. shr, ] P <0.001vs. shr ];
FIG. 3: serum Endothelin (ET) content of rats in each group [ in the figure, [ P <0.05vs. shr, [ P <0.01vs. shr, [ P <0.001vs. shr ];
FIG. 4: echocardiography of rat hearts of each group;
FIG. 5: left ventricular ejection fraction of rats in each group [ in the figure,. indicates P <0.05vs. shr,. indicates P <0.01vs. shr,. indicates P <0.001vs. shr ];
FIG. 6: left ventricular short axis shortening rate of rats in each group [ P <0.05vs. shr, [ P <0.01vs. shr, [ P <0.001vs. shr ].
Detailed Description
The present invention will be further described below with reference to specific examples, experimental examples and comparative examples, but is not limited thereto.
Example 1
A traditional Chinese medicine composition for treating hypertensive heart failure is prepared from the following raw material medicines in parts by weight: 15 parts of caulis spatholobi, 5 parts of pseudo-ginseng, 10 parts of salvia miltiorrhiza, 15 parts of astragalus mongholicus and 10 parts of pummelo peel, and the preparation method of the decoction is as follows:
1) pulverizing 15 parts of caulis Spatholobi, 5 parts of Notoginseng radix, 10 parts of Saviae Miltiorrhizae radix, 15 parts of radix astragali, and 10 parts of exocarpium Citri Grandis;
2) placing in a round-bottom flask, adding 50% methanol water solution 8 times the volume of the Chinese medicinal composition, heating and refluxing for 1h, and cooling;
3) placing in an ultrasonic water bath device, performing ultrasonic treatment at 50 deg.C for 60min under the ultrasonic power of 600W and frequency of 40KHz, and cooling;
4) taking supernatant, centrifuging at 3000r/min for 15min, and filtering to obtain filtrate.
Example 2
A traditional Chinese medicine composition for treating hypertensive heart failure is prepared from the following raw material medicines in parts by weight: 18 parts of suberect spatholobus stem, 6 parts of pseudo-ginseng, 12 parts of salvia miltiorrhiza, 18 parts of astragalus and 12 parts of pummelo peel, and the preparation method of the decoction comprises the following steps:
1) taking 18 parts of caulis spatholobi, 6 parts of pseudo-ginseng, 12 parts of salvia miltiorrhiza, 18 parts of astragalus mongholicus and 12 parts of pummelo peel, and crushing;
2) placing in a round-bottom flask, adding 6 times volume of 50% methanol aqueous solution of the Chinese medicinal composition, heating and refluxing for 1h, and cooling;
3) placing in an ultrasonic water bath device, performing ultrasonic treatment at 50 deg.C for 60min under the ultrasonic power of 600W and frequency of 40KHz, and cooling;
4) taking supernatant, centrifuging at 3000r/min for 15min, and filtering to obtain filtrate.
Example 3
A traditional Chinese medicine composition for treating hypertensive heart failure is prepared from the following raw material medicines in parts by weight: 12 parts of caulis spatholobi, 4 parts of pseudo-ginseng, 7 parts of salvia miltiorrhiza, 12 parts of astragalus mongholicus and 7 parts of pummelo peel, and the preparation method of the decoction is as follows:
1) taking the spatholobus stem, the pseudo-ginseng, the salvia miltiorrhiza, the astragalus mongholicus and the pummelo peel in parts by weight, and crushing;
2) placing in a round-bottom flask, adding 6 times volume of 50% methanol aqueous solution of the Chinese medicinal composition, heating and refluxing for 1h, and cooling;
3) placing in an ultrasonic water bath device, performing ultrasonic treatment at 50 deg.C for 60min under the ultrasonic power of 600W and frequency of 40KHz, and cooling;
4) taking supernatant, centrifuging at 3000r/min for 15min, and filtering to obtain filtrate.
Example 4
A traditional Chinese medicine composition for treating hypertensive heart failure is prepared from the following raw material medicines in parts by weight: 20 parts of caulis spatholobi, 8 parts of pseudo-ginseng, 15 parts of salvia miltiorrhiza, 20 parts of astragalus mongholicus and 15 parts of pummelo peel, and the preparation method of the decoction is as follows:
1) pulverizing 20 parts of caulis Spatholobi, 8 parts of Notoginseng radix, 15 parts of Saviae Miltiorrhizae radix, 20 parts of radix astragali, and 15 parts of exocarpium Citri Grandis;
2) placing in a round-bottom flask, adding 50% methanol water solution 12 times the volume of the Chinese medicinal composition, heating and refluxing for 1h, and cooling;
3) placing in an ultrasonic water bath device, performing ultrasonic treatment at 50 deg.C for 60min under the ultrasonic power of 600W and frequency of 40KHz, and cooling;
4) taking supernatant, centrifuging at 3000r/min for 15min, and filtering to obtain filtrate.
The decoction prepared in example 1 was used for animal experiments.
In animal experiments, the applicant compares the captopril which is the western medicine with the best curative effect and the widest application range at present, and verifies the treatment effect of the traditional Chinese medicine composition.
Captopril (Captopril) is an angiotensin converting enzyme inhibitor (ACE inhibitor or ACEI), which can directly inhibit the generation of local AT II of the heart while dilating blood vessels to reduce blood pressure, indirectly inhibit the release of catecholamine from sympathetic nerve endings of the heart on the other hand, and further reduce the activation of α or β receptors by catecholamine delivery, and prevent the occurrence of myocardial hypertrophy through the combined action of the two aspects, so that Captopril is applied to the treatment of hypertension and certain types of congestive heart failure.
The specific information for captopril is as follows:
chinese name: captopril. Chinese alias: 1- ((2S) -2-methyl-3-mercapto-1-oxopropyl) -L-proline; captoproline; (S) -1- (3-mercapto-2-methyl-1-oxopropyl) -L-proline; captopril; captopril; opening the fight; opening a forest; (ii) pribocong; captopril; carving on a fixed pattern; propionyl an arm; san Rayne captopril.
English name: captopril; english alias: dilabar; acepresss; lopril; sa 333; tensiomin; capoten; lopril; lopirin; SQ-14225; CAS number: 62571-86-2.
The molecular formula is as follows: c9H15NO3S。
Structural formula (xvi):
Figure BDA0001579022070000061
molecular weight: 217.28500, accurate mass: 217.07700, PSA: 96.41000, LogP: 0.56580.
experimental example 1
1. Laboratory animals and groups
Normal male WKY rats 7 and SHR21, 15 weeks old, 200-250 g weight, SPF grade, were provided by Beijing Wittingle laboratory animal technology Limited (license No.: SXK (Guangdong) 2016-.
Wherein SHR (Spontaneousy hypertensive rats) is obtained by mating a male Wistar Kyoto rat with the contraction pressure of 150-175 mmHg continuously with a female Wistar Kyoto rat with the contraction pressure of 130-140 mmHg to obtain offspring with the contraction pressure of more than 150mmHg, then selecting the rat with higher blood pressure for inbreeding, and sequentially carrying out the selective inbreeding for 20 generations to obtain stable hypertension inheritance, thereby establishing the SHR variety. The WKY is bred by Wistar rats, is used as a normal blood pressure control group animal of the SHR, is a control strain of hypertensive rats, and is suitable for relevant research of hypertension.
Experimental groups and specific drug feeding were as follows:
control (n ═ 7): for short, WKY group, male WKY rat, gavage 0.9% physiological saline;
model group (n ═ 7): abbreviated as SHR group, male SHR rat, gavage 0.9% normal saline;
a Chinese medicinal composition (n-7): for short, ZYZH group, male SHR rat, gavage 4.95g of crude drug/kg/d of example 1;
captopril group (n ═ 7): for CAP group, male SHR rat, gavage 13.5mg captopril/kg/d, as the positive control of western medicine.
All the drugs were prepared into solutions before the experiment at 1mL/100g body weight, and the solutions were administered by equal volume gavage, standard feed, free drinking water for 5 weeks.
2. Methods and results for detecting hypertension and heart failure
In the process of intragastric administration, the small animal noninvasive tail pressure instrument (ALC-NIBP) and a noninvasive blood pressure analysis system are used for detecting the systolic pressure of rats of each group every week, and the blood pressure level change of the rats is directly observed.
After 5 weeks of administration by gavage, each group extracted plasma through the tail vein of rats and centrifuged to obtain serum, and the content of NO and ET in the serum of rats was detected by using a kit for detecting NO and ET (Nanjing institute of bioengineering).
After 5 weeks of intragastric administration, rats were anesthetized with an intraperitoneal injection of urethane and the skin was prepared from the upper left chest to the lower clavicle to the lower rib margin. After the skin preparation is coated with couplant, a long-axis section of the heart is selected through an M-type echocardiogram, and the left ventricular Ejection Fraction (EF) and the left ventricular short-axis shortening (FS) of the rat are detected. Hypertensive heart failure causes a decline in left ventricular contractile function of the heart, and EF and FS are the first indicators for clinically judging left ventricular contractile ability, and thus can be used to evaluate the severity of heart failure.
The trend of the change of the Systolic Blood Pressure (SBP) of each group of rats is shown in table 1 and fig. 1; changes in NO and ET in serum are shown in table 2 and fig. 2, fig. 3; the echocardiography image is shown in figure 4; EF and ES are shown in table 3 and fig. 5 and 6, respectively.
TABLE 1 comparison of weekly systolic blood pressure (M + -SD) in rats of each group
Figure BDA0001579022070000081
Note:***represents P<0.001vs.SHR
TABLE 2 comparison (M + -SD) of serum Nitric Oxide (NO) and Endothelin (ET) in groups of rats at week five
Group of Serum NO (μmol/l) Serum ET (mu mol/l)
WKY group 41.63±1.08 103.1±1.9
SHR group 23.29±2.15 146.47±4.4
Group ZYZH 33.23±1.7** 126.1±4.69**
CAP group 38.95±2.34** 106.9±5.26***
Note:**represents P<0.01vs.SHR,***Represents P<0.001vs.SHR
TABLE 3 comparison of Ejection Fraction (EF) and short axis shortening (FS) of groups of rats at week five (M + -SD)
Group of EF(%) FS(%)
WKY group 80.4±2.7 60.4±3.29
SHR group 63.4±2.3 40.8±2.95
Group ZYZH 72.2±1.92*** 54.2±2.95***
CAP group 69±1.87** 48.6±2.3**
Note:**represents P<0.01vs.SHR,***Represents P<0.001vs.SHR
From the above results, it can be seen that: compared with the normal WKY group, the systolic pressure of the SHR group is obviously increased, the NO content in serum is reduced, and the ET content is increased, meanwhile, echocardiography shows that EF and FS of the SHR group are obviously reduced, which indicates that a rat model of hypertensive heart failure is successfully constructed, and after treatment of the traditional Chinese medicine combination group and the captopril group, the systolic pressure of a rat can be obviously reduced, NO in serum is increased, the ET content is reduced, and EF and FS of the rat are increased (P is less than 0.001). Wherein, EF and FS of the Chinese medicinal composition group are the largest, the effect is the best, and the EF and FS are respectively improved by 3.2 percent and 5.6 percent compared with CAP.
The research shows that[1-3]The traditional Chinese medicine composition has a good effect of improving the hypertensive heart failure, and the improvement effect in the aspect of the heart failure is better than that of captopril.
Comparative example 1
The Xuefu Zhuyu Tang is prepared from 11 Chinese medicinal materials including peach kernel, safflower, Ligusticum wallichii, radix paeoniae rubrathe, achyranthes and cyathula root, prepared rhizome of rehmannia, Chinese angelica root, bitter orange, root of ballon flower, Bupleurum root and licorice root, and has the functions of promoting blood circulation, removing blood stasis, promoting circulation of qi and relieving pain. Modern research shows that[4]The Xuefuzhuyu decoction can reduce the systolic pressure of spontaneous hypertension rats, wherein the blood pressure of rats in a Xuefuzhuyu decoction high dose group is 168.8 +/-13.3 mmHg after 5 weeks of intragastric administration, and the blood pressure reducing effect is reduced to 150.1 +/-3.3 mmHg after 5 weeks of intragastric administration, which is not the traditional Chinese medicine composition.
Comparative example 2
Zhen gan xie feng Tang, from Qing Dynasty's records of Yi Xue Zhong Can xi, is composed of 12 kinds of Chinese herbs including achyranthes root, Haematitum, raw dragon's bone, raw oyster, raw tortoise plastron, raw Hangzhou Shao, scrophularia root, asparagus cochinchinensis, toosendan fruit, raw malt, oriental wormwood, licorice root, etc., and has the effects of suppressing hyperactive liver, calming endogenous wind, nourishing yin and suppressing hyperactive yang. It can be used for treating apoplexy, vertigo, distention and tinnitus, and brain pain. Modern research shows that[5]: the liver-calming and wind-calming decoction can reduce the systolic blood pressure of spontaneous hypertensive rats, wherein the blood pressure of the rats after the liver-calming and wind-calming decoction is administrated by gastric administration for 4 weeks is 159 +/-6.3 mmHg, and the blood pressure reduction effect is close to that of the traditional Chinese medicine composition, but the liver-calming and wind-calming decoction is complex in formula and is not beneficial to further research and development.
The references mentioned in the examples and comparative examples are given below:
[1] wu Jinbo et al, the influence of the Chinese herbs for purging lung and inducing diuresis on the remodeling of the left ventricle of heart failure rats, journal of the university of transport of Western Ann (medical edition), 2017(01), p.136-141.
[2] Wangshenglin and Dong Yangrong, the influence of the water decoction of aconite root on the ventricular reconstruction of heart failure rat after myocardial infarction, Liaoning J.TCM 2010(S1), pp 243-245.
[3] Jiangbei et al, influence of the formula of purging the lung and inducing diuresis on blood pressure of spontaneously hypertensive rats, J.Zhonghua senile cardiovascular and cerebrovascular diseases, 2017(05), pp 529-531.
[4] Liuyue is equal, and the blood stasis removing decoction has influence on the blood vessel remodeling of spontaneous hypertension rats, TCM emergency 2015(08) page 1376 and 1379.
[5] Zhou Rong Feng, Jing Guang and Dan Qian, Zhen gan Xie Feng Tang have influence on blood pressure and serum free calcium of rats with spontaneous hypertension, Chinese Utility medicine, 2008(19), pp 31-32.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (9)

1. A traditional Chinese medicine composition is characterized by comprising the following raw material medicines: caulis Spatholobi, Notoginseng radix, Saviae Miltiorrhizae radix, radix astragali, and exocarpium Citri Grandis;
the raw material medicines are as follows in parts by weight: 10-20 parts of caulis spatholobi, 2-8 parts of pseudo-ginseng, 5-15 parts of salvia miltiorrhiza, 10-20 parts of astragalus membranaceus and 5-15 parts of pummelo peel.
2. The traditional Chinese medicine composition according to claim 1, wherein the raw material medicines comprise, by weight: 12-18 parts of caulis spatholobi, 4-6 parts of pseudo-ginseng, 7-13 parts of salvia miltiorrhiza, 12-18 parts of astragalus membranaceus and 7-13 parts of pummelo peel.
3. The traditional Chinese medicine composition according to any one of claims 1-2, wherein the active ingredient of the raw material drug is an extract of methanol aqueous solution, and the active ingredient of the raw material drug is subjected to ultrasonic treatment.
4. The traditional Chinese medicine composition according to claim 3, wherein: the traditional Chinese medicine composition is used for treating hypertension and/or heart disease, and the heart disease is hypertensive heart disease.
5. The traditional Chinese medicine composition according to claim 3, wherein: the traditional Chinese medicine composition also comprises pharmaceutically available auxiliary materials.
6. The traditional Chinese medicine composition according to claim 3, wherein: the dosage form of the traditional Chinese medicine composition is any one of the dosage forms in pharmaceutics.
7. The traditional Chinese medicine composition according to claim 6, wherein: the dosage form is decoction, pill, powder, tablet, granule or capsule.
8. The method for preparing the Chinese medicinal composition of any one of claims 1 to 7, which comprises the following steps:
(1) pulverizing caulis Spatholobi, Notoginseng radix, Saviae Miltiorrhizae radix, radix astragali, and exocarpium Citri Grandis as raw materials of the Chinese medicinal composition of any one of claims 1-7;
(2) adding 40% -50% v/v methanol aqueous solution 6-12 times the volume of the Chinese medicinal composition, heating, refluxing, extracting for 1-1.5h, and cooling to room temperature;
(3) subjecting the extractive solution to ultrasonic treatment at power of 600-800W, frequency of 40-50KHz and temperature of 40-50 deg.C for 50-60min, and cooling to room temperature;
(4) taking the supernatant, centrifuging at 3000-.
9. The method of claim 8, further comprising the steps of:
(5) adding adjuvants to obtain the Chinese medicinal composition.
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赵蒙.黄芪-丹参药对对自发性高血压大鼠肾损害的干预研究.《中国中西医结合学会肾脏疾病专业委员会2015年学术年会资料汇编》.2015,第978页最后一段. *
黄芪-丹参药对对自发性高血压大鼠肾损害的干预研究;赵蒙;《中国中西医结合学会肾脏疾病专业委员会2015年学术年会资料汇编》;20151015;第978页最后一段 *

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